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[大学生论坛]:[大学生论坛]:微生物遗传成分调节宿主寿命

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JoannaH 发表于 2018-1-2 14:18:50 | 显示全部楼层 |阅读模式
Microbial Genetic Composition Tunes Host Longevity.

微生物遗传成分调节宿主寿命

Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPR(mt)) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPR(mt)-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.

肠道菌群的动态平衡严重影响宿主健康和老龄化,因此开发基因工程益生菌有望成为促进健康老龄化的新的治疗模式。通过筛选3983个大肠杆菌突变体,在筛选29个细菌基因时,我们发现秀丽隐杆线虫可以增加寿命。十几种细菌突变体也能保护宿主避免肿瘤生长和淀粉样β累积的年龄依赖性增长。具体来说,我们发现五的细菌突变体促进长寿的多糖colanic酸分泌增加(CA),调节线粒体动力学和未折叠蛋白反应(UPR(MT))在主机。纯化的CA的聚合物是足以通过ATFS-1延年益寿,主机UPR(MT)-反应转录因子。此外,CA诱导的线粒体变化和长寿效应在不同物种间是保守的。我们的研究结果确定了开发长寿命微生物的分子靶标和一种作用于宿主线粒体的细菌代谢产物,用于促进长寿。

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